Objectives: Complement activation is a critical feature in the development of systemic lupus erythematosus (SLE). Whether there are changes of complement components in the urine of SLE has not been reported. The aim of the study was to evaluate the complement-related proteins in the urine of SLE, verify differentially expressed proteins(DEPs) in the active phase of SLE, further explore their clinical application value.
Methods: First, we used bioinformatics and functional enrichment to screen and identify the urine protein profile of SLE patients. Then, analyzed and verified the proteins related to the complement pathway by western-blot and Parallel Reaction Monitoring (PRM) technology. Further evaluated the relationship between urinary DEPs related to complement pathway and disease activity.
Results: A total of 14 complement pathway-related proteins were screened for differences in expression between the active group and the stable group, eight of these DEPs were up-regulated and six were down-regulated. These DEPs may play a key role in SLE disease activity. We used PRM technology to verify the eight up-regulated proteins, and found that four of these complement proteins, namely C9, C8A, C4B, and C8G, were significantly increased in active group. Furthermore, these four DEPs were highly correlated with disease activity. In the urine of SLE patients, AUCs of 0.750, 0.840, 0.757 and 0.736 were achieved with C9, C8A, C4B, and C8G, respectively.
Conclusions: Complement-related DEPs in urine have a certain correlation with SLE disease activity. Urine C9, C8A, C4B and C8G present promising non-invasive biomarkers for monitoring lupus activity.
Keywords: Biomarker; Complement; Differentially expressed proteins; Lupus; Urine.
©2022 Zhao et al.